Chromatin associated SETD3 negatively regulates VEGF expression.
Chromatin associated SETD3 negatively regulates VEGF expression.
复制标题
染色质相关的setD3负调节VEGF表达。
DOI：
10.1038/srep37115
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发表时间：
2016-11-15
影响因子：
4.6
通讯作者：
Levy D
中科院分区：
文献类型：
--
作者：
Cohn O;Feldman M;Weil L;Kublanovsky M;Levy D
SETD3 是蛋白质赖氨酸甲基转移酶 (PKMT) 家族的成员，可催化向赖氨酸残基添加甲基。越来越多的数据表明，PKMT 通过靶向组蛋白和非组蛋白参与广泛的生物过程的调节。使用蛋白质组学方法，我们鉴定了 172 个新的 SETD3 相互作用蛋白。我们发现 SETD3 结合转录因子 FoxM1 并使其甲基化，该因子先前已被证明与 VEGF 表达的调节有关。我们进一步证明在缺氧条件下 SETD3 下调。从机制上讲，我们发现在基础条件下，SETD3 和 FoxM1 在 VEGF 启动子上富集。缺氧条件下 SETD3 和 FoxM1 从 VEGF 启动子上解离与 VEGF 表达升高相关。总而言之，我们的数据揭示了染色质上一个新的 SETD3 依赖的基于甲基化的信号通路，该通路在常氧和缺氧条件下调节 VEGF 表达。
SETD3 is a member of the protein lysine methyltransferase (PKMT) family, which catalyzes the addition of methyl group to lysine residues. Accumulating data suggest that PKMTs are involved in the regulation of a broad spectrum of biological processes by targeting histone and non-histone proteins. Using a proteomic approach, we have identified 172 new SETD3 interacting proteins. We show that SETD3 binds and methylates the transcription factor FoxM1, which has been previously shown to be associated with the regulation of VEGF expression. We further demonstrate that under hypoxic conditions SETD3 is down-regulated. Mechanistically, we find that under basal conditions, SETD3 and FoxM1 are enriched on the VEGF promoter. Dissociation of both SETD3 and FoxM1 from the VEGF promoter under hypoxia correlates with elevated expression of VEGF. Taken together, our data reveal a new SETD3-dependent methylation-based signaling pathway at chromatin that regulates VEGF expression under normoxic and hypoxic conditions.
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